The long term objective is the investigation of the physiology of the retinal circulation and of the role played by this circulation in the development of diabetic retinopathy. We will investigate: A. Normal physiology a) The regulation of retinal blood flow (RBF) in response to light/dark transition; b) The regulation of RBF in response to changes in arterial blood oxygen concentration; c) The regulation of RBF in response to changes in perfusion pressure; d) The physiologic principles of optimality underlying retinal arterial branching, radii and flows. B. Diabetic retinopathy a) The prognostic significance and natural history of changes in RBF and blood flow regulation to 100% O2 breathing; b) The correlation between RBF and its regulation to 100% O2, breathing and the electroretinographic oscillatory potentials; c) The correlation between RFB and its regulation to 100% O2, breathing and the clinical response to panretinal laser photocoagulation; d) The effect of an acute drop of blood sugar due to insulin treatment on RBF and its regulation to 100% O2 breathing. These goals will be achieved through the use of Laser Doppler Velocimetry (LDV) and Monochromatic Fundus Photography combined, for the first time, with simultaneous measurements of preretinal PO2. It is hoped that these studies, which blend the efforts of basic scientists and clinicians, will provide a better understanding of the physiology of the retinal circulation and of the microvascular pathophysiology in diabetic retinopathy through a better understanding of the mechanisms underlying retinal vascular responses. This understanding together with the development of new ways of testing RBF regulation may improve the monitoring of the progression of the disease and of the effect of treatment.